教師簡介

  • 專任副教授
  • 李曉暉
  • Hsiao-Hui Lee
  • (O)02-2826-7205/(Lab)02-2826-7000 ext. 6257 or 6213
  • hhl@ym.edu.tw
  • 圖書資訊暨研究大樓9樓R923、R926
  • 專業領域
  • 分子生物學、細胞生物學、細胞生物力學
  • 研究方向
  • 對於貼附於細胞外基質 (ECM) 的細胞而言,透過細胞膜上的Integrin與細胞外基質間的相互作用對於細胞的生長、分化或移動等活性的調控是非常重要的。當Integrin與細胞外基質產生連結時, 細胞膜內側許多蛋白質會形成一複合體,並與肌動蛋白纖維連接,形成所謂的黏著焦點 (FA) ,藉此傳達細胞外基質與細胞骨架間的作用力。細胞中肌動蛋白纖維 (actin filaments) 的收縮力 (actomyosin contractility) 主要是受到RhoA-ROCK訊息所調控的,在我們的研究中發現Shp2這個去磷酸酶會透過與alpha-actinin-4作用分佈到FA,促進ROCK被RhoA 活化以增強細胞黏著焦點與肌動蛋白纖維的整合,進而增強細胞內張力以因應ECM硬度的增加。文獻報告中指出人類alpha- actinin-4的基因ACTN4突變造成腎小球病變(FSGS),因此我們進一步利用腎小球執行血液過濾的關鍵足細胞 (podocytes)進行研究,利用CRISPR/Cas9的方法建立了ACTN4基因剔除足細胞,證實alpha-actinin- 4在足細胞中對Shp2活化是重要的,透過ROCk2所調控的張力,促進足細胞的附著力以及細胞骨架的維持,而對足細胞的過濾功能扮演關 鍵角色。我們將與榮總腎臟科團隊合作,從基礎到臨床探討與腎小球病變有關的基因與分子機制,並建立模擬過濾裝置,探討腎臟足細胞的力訊息 傳遞。此外,我們利用利用跨領域科學方法,以不同張力耐受性單分子受力模組,可以成功地偵測細胞斑增大以及YAP分子進入細胞核的張力需 求。

  • 教授科目
  • 生命科學總論(上)
    細胞生物學
    普通生物學
    生命科學實驗(二)
    生命科學實驗(三)
    生化及細胞分子生物學(二)
    細胞骨架力學
    跨領域科學在細胞移動研究之應用
    生命科學技術
  • 經歷
  • 2015 Feb.-present
    國立陽明大學
    生命科學系暨基因體科學研究所
    副教授
  • 2013 Aug.-2015 Jan.
    國立陽明大學
    生命科學系暨基因體科學研究所
    助理教授
  • 2009 Aug.-2013 Jul.
    國立陽明大學
    生命科學系暨基因體科學研究所
    專案助理教授
  • 2011 Apr., Jul.-Sep., and 2012 Jan.-Feb.
    美國加州大學聖地牙哥分校
    醫學工程研究所
    訪問學者
  • 2006 Feb.-2009 Jul.
    國立臺灣大學
    生物化學暨分子生物學研究所
    博士後研究
  • 學歷
  • 2006 Jan.
    國立臺灣大學
    生物化學暨分子生物學研究所
    博士

代表著作

    期刊論文
  • Lisowska J, Rödel CJ, Manet S, Miroshnikova YA, Boyault C, Planus E, De Mets R, Lee HH, Destaing O, Mertani H, Boulday G, Tournier-Lasserve E, Balland M, Abdelilah-Seyfried S, Albiges-Rizo C, Faurobert E. L. The CCM1-CCM2 complex controls complementary functions of ROCK1 and ROCK2 that are required for endothelial integrity. J Cell Sci. 2018 Aug 13;131(15). pii: jcs216093. doi: 10.1242/jcs.216093.
  • Jheng GW, Hur SS, Chang CM, Wu CC, Cheng JS, Lee HH, Chung BC, Wang YK, Lin KH, Del Álamo JC, Chien S, Tsai JW. Lis1 dysfunction leads to traction force reduction and cytoskeletal disorganization during cell migration. Biochem Biophys Res Commun. 2018 Mar 11;497(3):869-875. doi: 10.1016/j.bbrc.2018.02.151.
  • Chang CH, Lee HH*, Lee CH*. Substrate properties modulate cell membrane roughness by way of actin filaments. Sci Rep. 2017 Aug 22;7(1):9068. doi: 10.1038/s41598-017-09618-y (*corresponding author)
  • Wu TH, Kuo YY, Lee HH, Kuo JC, Ou MH, Chang ZF*. Epigenetic repression of ribosomal RNA transcription by ROCK-dependent aberrant cytoskeletal organization. Sci Rep. 2016 Jun 28;6:28685. doi: 10.1038/srep28685.
  • Tien SC, Lee HH, Yang YC, Lin MH, Chen YJ, Chang ZF*. Inhibition of HDAC6 reverses oncogenic Shp2-induced epithelial lumenogenesis defect independent of Cdc42. Nature Communications. 2016 Jan 19;7:10420. doi: 10.1038/ncomms10420.
  • Hsu CY, Chang ZF, and Lee HH*. Immunohistochemical evaluation of ROCK activation in invasive breast cancer. BMC Cancer. 2015 Dec 1;15(1):943. doi: 10.1186/s12885-015-1948-8. (*corresponding author)
  • Liu NY, Lee HH, Chang ZF, Tsay YG*. Examination of segmental average mass spectra from liquid chromatography-tandem mass spectrometric (LC-MS/MS) data enables screening of multiple types of protein modifications. Anal Chim Acta. 2015 Sep 10;892: 115-22. doi: 10.1016/j.aca.2015.07.032.
  • Wang HL, Yang CH, Lee HH, Kuo JC, Hur SS, Chien S, Lee KS, Hung SH, Chang ZF*. Dexamethasone-induced SGK1 increases Sec5/GEF-H1 interaction essential for adhesion-mediated tension. J Cell Sci. 2015 Oct 15;128(20):3757-68. doi: 10.1242/jcs.169961.
  • Tsai IJ, Chou CH, Yang YH, Lin WC, Lin YH, Chow LP, Lee HH, Kao PG, Liau WT, Jou TS*, Tsau YK*. Inhibition of Rho-associated kinase relieves C5a induced proteinuria in murine nephrotic syndrome. Cell Mol Life Sci. 2015 Aug;72(16):3157-71. doi: 10.1007/s00018-015-1888-0.
  • Kuo YC, Chang TH, Hsu WT, Zhou J, Lee HH, Ho HC, Chien S, and Lee KS*. Oscillatory shear stress mediates directional re-organization of actin cytoskeleton and alters differentiation propensity of mesenchymal stem cells. Stem Cells. 2015 Feb;33(2):429-42. doi: 10.1002/stem.1860.
  • Chuang HH, Liang SW, Chang ZF*, and Lee HH*. Ser1333 phosphorylation indicates ROCKI activation. J Biomed Sci. 2013 Oct 29;20:83. doi: 10.1186/1423-0127-20-83. (*corresponding author)
  • Lee HH*, Lee HC, Chou CC, Hur SS, Osterday K, del Álamo JC, Lasheras JC, and Chien S*. Shp2 plays a crucial role in cell structural orientation and force polarity in response to matrix rigidity. Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):2840-5. doi: 10.1073/pnas.1222164110. (* corresponding author)
  • Pan YR, Cho KH, Lee HH, Chang ZF, and Chen HC. Protein tyrosine phosphatase SHP2 suppresses podosome rosette formation in Src-transformed fibroblasts. J Cell Sci. 2013 Jan 15;126(Pt 2):657-66. doi: 10.1242/jcs.116624.
  • Chuang HH , Yang CH, Tsay YG, Hsu CY, Tseng LM, Chang ZF*, Lee HH*. ROCKII serine 1366 phosphorylation reflects the activation status. Biochem J. 2012 Apr 1;443(1):145-51. doi: 10.1042/BJ20111839. (*corresponding authors)
  • Lee HH, Tien SC, Jou TS, Chang YC, Jhong JG, and Chang ZF. c-Src-dependent phosphorylation of ROCK participates in regulation of focal adhesion dynamics. J Cell Sci. 2010 Oct 1;123(Pt 19):3368-77. doi: 10.1242/jcs.071555.
  • Lee HH and Chang ZF. Regulation of RhoA-dependent ROCKII activation by Shp2. J Cell Biol. 2008 Jun 16;181(6):999-1012. doi: 10.1083/jcb.200710187. (Faculty of 1000 in Biology, Recommended)
  • Chang YC, Lee HH, Chen YJ, Bokoch G and Chang, ZF. Contribution of guanine exchange factor H1 in phorbol ester-induced apoptosis. Cell Death Differ. 2006 Dec;13(12):2023-32.
  • Chang ZF and Lee HH. RhoA signaling in phorbol ester-induced apoptosis. J Biomed Sci. 2006 Mar;13(2):173-80. (Review)
  • Lee HH, Chien CL, Liao HK, Chen YJ, and Chang ZF. Nuclear efflux of heterogeneous nuclear ribonucleoprotein C1/C2 in apoptotic cells: a novel nuclear export dependent on Rho-associated kinase activation. J Cell Sci. 2004 Nov 1;117(Pt 23):5579-89.
  • Lai LP, Lin JL, Lin CS, Yeh HM, Tsay YG, Lee CF, Lee HH, Chang ZF, Hwang JJ, Su MJ, Tseng YZ, Huang SK. Functional genomic study on atrial fibrillation using cDNA microarray and two-dimensional protein electrophoresis techniques and identification of the myosin regulatory light chain isoform reprogramming in atrial fibrillation. J Cardiovasc. Electrophysiol. 2004 Feb;15(2):214-23.
  • Lin CM, Chen CT, Lee HH, Lin JK. Prevention of cellular ROS damage by isovitexin and related flavonoids. Planta Med. 2002 Apr;68(4):365-7.

    專利與技轉

  • 專利名稱:Reagents for probing ROCKs activation.
    發明人:Zee-Fen CHANG, Hsiao-Hui Lee
    公告號 (TW):I460274 (Taiwan patent approved at 2014)
    公開號 (US):US9017952 B2 (US patent approved at 2015)
    技轉:億康生物科技有限公司